A combined observational and Mendelian randomization investigation reveals NMR-measured analytes to be risk factors of major cardiovascular diseases.

Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.

The association between alcohol consumption and blood lipids in Chinese children and adolescent: findings from the China Health and Nutrition Survey.

BACKGROUND: Alcohol consumption by children and adolescents is receiving increasing attention. It may cause dyslipidemia, a risk factor for cardiovascular disease. However, the association between alcohol consumption and blood lipids in children and adolescents is unclear, and so we aimed to characterize this association. METHODS: Data from the China Health and Nutrition Survey were extracted from children and adolescents aged 7-18 years for whom information was available on alcohol consumption. The population was divided into drinking and nondrinking groups. The χ2, Student's t, or Mann-Whitney U test was used to compare groups. Univariate and multivariate linear regression and propensity score matching (PSM) analysis were used to identify the association between alcohol consumption and blood lipids. RESULTS: This study included 408 children and adolescents with 35 drinkers and 373 nondrinkers. The drinkers had significantly lower values of total cholesterol (TC) (3.8 mmol/L for nondrinkers versus 3.5 mmol/L for drinkers, p = 0.002) and high-density lipoprotein cholesterol (HDL-C) (1.3 mmol/L for nondrinkers versus 1.2 mmol/L for drinkers, p = 0.007), but not for low-density lipoprotein cholesterol (LDL-C) (2.1 mmol/L for nondrinkers versus 2.0 mmol/L for drinkers, p = 0.092) or triglyceride (TG) (0.9 mmol/L for nondrinkers versus 0.8 mmol/L for drinkers, p = 0.21). The univariate and multivariate analyses led to the same conclusions. After PSM there was still a significant negative association between alcohol consumption and TC or HDL-C. CONCLUSION: Alcohol consumption in children and adolescents exhibited significant negative associated with TC and HDL-C, but not with LDL-C or TG. These findings need to be confirmed in future prospective research, and the health effects of blood lipid changes caused by drinking in children and adolescents need to be clarified.

Lipids as potential mediators linking body mass index to diabetes: evidence from a mediation analysis based on the NAGALA cohort.

BACKGROUND: Body mass index (BMI) and lipid disorders are both known to be strongly associated with the development of diabetes, however, the indirect effect of lipid parameters in the BMI-related diabetes risk is currently unknown. This study aimed to investigate the mediating role of lipid parameters in the association of BMI with diabetes risk. METHODS: We assessed the association of diabetes risk with BMI, as well as lipid parameters including high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-CF and LDL-CS), triglycerides(TG), total cholesterol(TC), remnant cholesterol(RC), non-HDL-C, and combined indices of lipid parameters with HDL-C (RC/HDL-C ratio, TG/HDL-C ratio, TC/HDL-C ratio, non-HDL/HDL-C ratio, LDL/HDL-C ratio) using data from 15,453 subjects in the NAGALA project. Mediation models were used to explore the mediating role of lipid parameters in the association of BMI with diabetes risk, and mediation percentages were calculated for quantifying the strength of the indirect effects. Finally, receiver operating characteristic curve (ROC) analysis was used to compare the accuracy of BMI and BMI combined with lipid parameters in predicting incident diabetes. RESULTS: Multivariate regression models, adjusted for confounding factors, demonstrated robust associations of lipid parameters, BMI, with diabetes risk, with the exception of TC, LDL-CF, LDL-CS, and non-HDL-C. Mediation analysis showed that lipid parameters except TC, LDL-CF, LDL-CS, and Non-HDL-C were involved in and mediated the association of BMI with diabetes risk, with the largest mediation percentage being the RC/HDL-C ratio, which was as high as 40%; it is worth mentioning that HDL-C and HDL-C-related lipid ratio parameters also play an important mediating role in the association between BMI and diabetes, with the mediator proportion being greater than 30%. Finally, based on the ROC results, we found that the prediction performance of all lipid parameters in the current study except TC was significantly improved when combined with BMI. CONCLUSION: Our fresh findings suggested that lipid parameters partially mediated the association of BMI with diabetes risk; this result indicated that in the context of diabetes risk screening and disease management, it is important to not only monitor BMI but also pay attention to lipid parameters, particularly HDL-C and HDL-C-related lipid ratio parameters.

Association between HDL cholesterol with diabetic retinopathy in diabetic patients: a cross-sectional retrospective study.

OBJECTIVE: Diabetic patients are often comorbid with dyslipidemia, however, the relationship between high-density lipoprotein cholesterol(HDL-C) and diabetic retinopathy (DR) in the adult diabetic population remains to be fully elucidated.The aim of this study is to evaluate the associations between HDL-C and DR in the United States adults with diabetes. METHODS: A total of 1708 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008 were enrolled in the present study. Fundus images of all study subjects were captured and evaluated using a digital camera and an ophthalmic digital imaging system, and the diagnosis of DR was made by the severity scale of the Early Treatment Diabetic Retinopathy Study (ETDRS).Roche Diagnostics were used to measure serum HDL-C concentration. The relationship of DR with HDL-C was investigated using multivariable logistic regression. The potential non-line correlation was explored with smooth curve fitting approach. RESULTS: The fully-adjusted model showed that HDL-C positively correlated with DR(OR:1.69, 95%CI: 1.25-2.31).However, an inverted U-shaped association between them was observed by applying the smooth curve fitted method. The inflection point of HDL-C(1.99mmol/l) was calculated by utilizing the two-piecewise logistic regression model. In the subgroup analysis, the inverted U-shaped nonlinear correlation between HDL-C and DR was also found in female, Non-Hispanic White, and lower age groups. CONCLUSION: Our study revealed an inverted U-shaped positive relationship between HDL-C and DR.The findings may provide us with a more comprehensive understanding of the association between HDL-C and DR.

Resilient Older Subjects with Heterozygous Familial Hypercholesterolemia, Baseline Differences and Associated Factors.

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL; p < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.

Association between gamma glutamyl transpeptidase to HDL-Cholesterol (GGT/HDL-C) ratio and metabolic syndrome resolution after sleeve gastrectomy.

OBJECTIVE: To evaluate the association between GGT/HDL-C ratio and resolution of MetS in adults after sleeve gastrectomy (SG). METHODS: We conducted a retrospective cohort study using secondary data from a Peruvian bariatric center. The study population consisted of adults aged 18 and above who underwent laparoscopic SG and were diagnosed with MetS prior to the surgery. The main outcome measured was MetS resolution 6 months post-surgery and the exposure variable was the GGT/HDL-C ratio. RESULTS: We analyzed 137 patients with a mean age of 38.9 ± 10.9 years; 64.2% were females. The median GGT/HDL-C ratio was 1.1 [0.7 - 1.5], and 83.9% of patients experienced resolution of MetS. Furthermore, both the middle tertile of GGT/HDL-C (aRR: 1.28; 95% CI: 1.04 - 1.58; p = .019) and the lowest tertile (aRR: 1.27; 95% CI: 1.01 - 1.60; p = .038) showed a significant association with the resolution of MetS. CONCLUSION: Eight out of 10 patients undergoing SG experience resolution of MetS within 6 months after surgery. Patients in the middle and lower tertiles of the GGT/HDL-C were more likely to achieve this outcome. Therefore, the GGT/HDL-C ratio should be considered a valuable and efficient biomarker for preoperative assessment of bariatric surgery candidates.

Lipids, apolipoproteins and gestational diabetes mellitus: a Mendelian randomization study.

BACKGROUND: This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM. METHODS: Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment. RESULTS: Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI). CONCLUSION: The study demonstrates a significant causal relationship between apoA-I and GDM risk.

Biomarker signatures associated with ageing free of major chronic diseases: results from a population-based sample of the EPIC-Potsdam cohort.

BACKGROUND: A number of biomarkers denoting various pathophysiological pathways have been implicated in the aetiology and risk of age-related diseases. Hence, the combined impact of multiple biomarkers in relation to ageing free of major chronic diseases, such as cancer, cardiovascular disease and type 2 diabetes, has not been sufficiently explored. METHODS: We measured concentrations of 13 biomarkers in a random subcohort of 2,500 participants in the European Prospective Investigation into Cancer and Nutrition Potsdam study. Chronic disease-free ageing was defined as reaching the age of 70 years within study follow-up without major chronic diseases, including cardiovascular disease, type 2 diabetes or cancer. Using a novel machine-learning technique, we aimed to identify biomarker clusters and explore their association with chronic disease-free ageing in multivariable-adjusted logistic regression analysis taking socio-demographic, lifestyle and anthropometric factors into account. RESULTS: Of the participants who reached the age of 70 years, 321 met our criteria for chronic-disease free ageing. Machine learning analysis identified three distinct biomarker clusters, among which a signature characterised by high concentrations of high-density lipoprotein cholesterol, adiponectin and insulin-like growth factor-binding protein 2 and low concentrations of triglycerides was associated with highest odds for ageing free of major chronic diseases. After multivariable adjustment, the association was attenuated by socio-demographic, lifestyle and adiposity indicators, pointing to the relative importance of these factors as determinants of healthy ageing. CONCLUSION: These data underline the importance of exploring combinations of biomarkers rather than single molecules in understanding complex biological pathways underpinning healthy ageing.

Association of non-insulin-based insulin resistance indices with disease severity and adverse outcome in idiopathic pulmonary arterial hypertension: a multi-center cohort study.

BACKGROUND: Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. METHODS: A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. RESULTS: During a mean of 3.6 years' follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P < 0.001) were significantly increased in high to intermediate-high risk patients. IR indices correlated with well-validated variables that reflected the severity of IPAH, such as the cardiac index and stroke volume index. Multivariate Cox regression analyses indicated that the TyG-BMI index (hazard ratio [HR] 1.179, 95% confidence interval [CI] 1.020, 1.363 per 1.0-standard deviation [SD] increment, P = 0.026) and METS-IR (HR 1.169, 95% CI 1.016, 1.345 per 1.0-SD increment, P = 0.030) independently predicted adverse outcomes. Addition of the TG/HDL-C ratio and METS-IR significantly improved the reclassification and discrimination ability beyond the European Society of Cardiology (ESC) risk score. CONCLUSIONS: IR is associated with the severity and long-term prognosis of IPAH. TyG-BMI and METS-IR can independently predict clinical worsening events, while METS-IR also provide incremental predictive performance beyond the ESC risk stratification.

Different association of atherogenic index of plasma with the risk of high platelet reactivity according to the presentation of acute myocardial infarction.

This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96-0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96-1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P < 0.05). AIP levels were not independently associated with the risk of composite outcomes in both patients with non-AMI and AMI. In conclusion, an inverse association between AIP and the risk of HPR was observed in patients with non-AMI. This suggests that the association between plasma atherogenicity and platelet reactivity may play a substantial role in the development of AMI.Trial registration: NCT04734028.

Association between lipid profiles and cigarette smoke among adults in the Persian cohort (Shahedieh) study.

OBJECTIVES: Exposure to cigarette smoke introduces a large amount of nicotine into the bloodstream through the lungs. So, smoking can be a risk factor for many diseases. The present study was conducted to investigate the effect of active and passive cigarette smoke on the blood lipid profile and dyslipidemia. METHODS: This cross-sectional study was performed on 5052 individuals who participated in the recruitment phase of the Shahedieh cohort study. A logistic regression model was used to investigate the relationship between smoking exposure status and lipid profiles. RESULTS: The prevalence of abnormal low-density lipoprotein-cholesterol (LDL-C), abnormal HDL-C, abnormal total cholesterol (TC), abnormal triglyceride (TG), and dyslipidemia were 254 (5.00%), 562 (11.10%), 470 (9.30%), 1008 (20.00%), and 1527 (30.20%), respectively. Adjusting for confounders, it was observed that current smokers had higher odds of having abnormal HDL-C [OR (95% CI), 2.90 (2.28-3.69)], abnormal TG [OR (95% CI), 1.71 (1.38-2.13)] and dyslipidemia [OR (95% CI), 1.86 (1.53-2.25)]. Ex-smokers also had greater odds of abnormal HDL-C [OR (95% CI), 1.51 (1.06-2.16)] compared to non-smokers who were not exposed to cigarette smoke. CONCLUSIONS: The findings indicated that current smokers had higher TG and lower HDL. So, necessary measures should be taken to reduce smoking. The findings also showed that the prevalence of abnormal TG and HDL in ex-smokers was lower than in current smokers. Therefore, the existence of incentive policies to quit smoking seems necessary.

The effect of lipid-lowering therapy on lipid-related residual risk factors: a prospective study.

BACKGROUND: Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. METHODS: This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. RESULTS: Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P < 0.001), apoB (-19.35% vs. -3.17%, P < 0.001), triglycerides (-17.82% vs. -6.62%, P < 0.001), and LDL-C and total cholesterol. Spearman correlation analysis revealed that LDL-C reduction from current LLT was strongly correlated with nonHDL-C reduction (r = 0.87, P < 0.001). Patients who received high-intensity LLT had significant improvements in attainment of RC (from 44.2% to 60.7%, χ² = 39.23, P < 0.001) and nonHDL-C (from 19.4% to 56.9%, χ² = 226.06, P < 0.001) goals. Furthermore, multivariate logistic regression showed that high-intensity LLT was a protective factor for RC [odds ratio (OR) = 0.66; 95% confidence intervals (CI), 0.45-0.97; P = 0.033] and nonHDL-C goal attainment (OR = 0.51; 95% CI, 0.34-0.75; P < 0.001), without a significant increase of adverse reactions. CONCLUSION: Current levels of clinically prescribed LDL-C-centric treatment can reduce RC and other lipid-related residual risk factors, but high-intensity LLT is better at achieving nonHDL-C and RC goals than low-/moderate-intensity LLT, with a good safety profile. More targeted RC treatments are still needed to reduce residual lipid risk further.

Causal relationship between dyslipidemia and risk of facial aging: Insights from Mendelian randomization in East Asian populations.

BACKGROUND: Emerging observational studies showed an association between dyslipidemia and aging. However, it remains unclear whether this association is causal, particularly in the case of Asians, which are aging more rapidly than other continents. Given the visible manifestations of aging often include changes in facial appearance, the objective of this study is to assess the causal relationship between dyslipidemia and facial aging in East Asian populations. METHODS: SNPs related to dyslipidemia in East Asian people such as Total cholesterol (TC), High-density-lipoprotein cholesterol (HDL), Low-density-lipoprotein cholesterol (LDL), and Triglyceride (TG) along with outcomes data on facial aging, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse variance weighted (IVW) method. RESULTS: Totally, 88 SNPs related to HDL among 70657 East Asian participants in GWAS. Based on the primary causal effects model using MR analyses with the IVW method, high HDL level was demonstrated as significantly related to the risk of facial aging (OR, 1.060; 95% CI, 1.005-1.119, p = 0.034), while high TC level (OR, 0.995; 95% CI, 0.920-1.076, p = 0.903), high LDL level (OR, 0.980, 95% CI, 0.924-1.041, p = 0.515), as well as high TG level (OR, 0.999, 95% CI, 0.932-1.071, p = 0.974), showed no significant correlation with facial aging. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between high HDL levels and facial aging. In contrast, facial aging demonstrated no significant correlation with high levels of TC, LDL, or TG. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding nutrition management to delay the aging process among old patients in East Asia.

The chain-mediating effect of Crp, BMI on the relationship between dietary intake of live microbes and hyperlipidaemia.

BACKGROUND: Inflammation and obesity are the risk factors for hyperlipidaemia. Nonetheless, research regarding the association between dietary live microbes intake and hyperlipidaemia is lacking. Therefore, this study focused on revealing the relationship between them and mediating roles of inflammation and obesity. METHODS: Totally 16,677 subjects were enrolled from the National Health and Nutrition Examination Survey (NHANES) (1999-2010 and 2015-2020). To explore the correlation between live microbes and hyperlipidaemia as well as blood lipid levels, respectively, multiple logistic regression and linear regression were employed. Furthermore, the mediating roles of body mass index (BMI), C-reactive protein (Crp) and their chain effect were explored through mediating analysis. RESULTS: High dietary live microbes intake was the protective factor for hyperlipidaemia. In addition, high dietary live microbes intake exhibited a positive relationship to the high-density lipoprotein cholesterol (HDL-C) among males (ß = 2.52, 95% CI: 1.29, 3.76, P < 0.0001) and females (ß = 2.22, 95% CI: 1.05, 3.38, P < 0.001), but exhibited a negative correlation with triglyceride (TG) levels in males (ß = -7.37, 95% CI: -13.16, -1.59, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) levels in females (ß = -2.75, 95% CI: -5.28, -0.21, P = 0.02). Crp, BMI and their chain effect mediated the relationship between live microbes with HDL-C levels. Moreover, BMI and the chain effect mediated the relationship between live microbes with LDL-C levels. CONCLUSION: Dietary live microbes intake is related to a lower hyperlipidaemia risk. Crp, BMI and their chain effect make a mediating impact on the relationship.

Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study.

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver-MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis-MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

Comparative Safety and Efficacy of Low/Moderate-Intensity Statin plus Ezetimibe Combination Therapy vs. High-Intensity Statin Monotherapy in Patients with Atherosclerotic Cardiovascular Disease: An Updated Meta-Analysis.

AIM: Statin therapy is considered the gold standard for treating hypercholesterolemia. This updated meta-analysis aims to compare the efficacy and safety of a low/moderate-intensity statin in combination with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (ASCVD). METHODS: A systematic search of two databases (PubMed and Cochrane CENTRAL) was conducted from inception to January 2023 and a total of 21 randomized clinical trials (RCTs) were identified and included in the analysis. Data were pooled using Hedges's g and a Mantel-Haenszel random-effects model to derive standard mean differences (SMDs) and 95% confidence intervals (Cis). The primary outcome studied was the effect of these treatments on lipid parameters and safety events. RESULTS: The results revealed that combination therapy was more effective in reducing low-density lipoprotein cholesterol (LDL-C) levels (SMD= - 0.41; CI - 0.63 to - 0.19; P = 0.0002). There was no significant change in the levels of high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), triglyceride (TG), high-sensitivity C-reactive protein (hs-CRP), Apo A1, or Apo B. The safety of these treatments was assessed by the following markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine phosphokinase (CK), and a significant difference was only observed in CK (SMD: - 0.81; CI - 1.52 to - 0.10; P = 0.02). CONCLUSION: This meta-analysis demonstrated that the use of low/moderate-intensity statin combination therapy significantly reduced LDL-C levels compared with high-intensity statin monotherapy, making it preferable for patients with related risks. However, further trials are encouraged to evaluate potential adverse effects associated with combined therapy.

The association of ALT to HDL-C ratio with type 2 diabetes in 50-74 years old adults: a population-based study.

There is limited information about the relationship between diabetes mellitus (DM) and ALT to HDL-C ratio. This study aims to investigate this relationship for the first time in Iran. The data of this study were taken from the third phase of the Shahroud Eye Cohort Study, which was conducted in 2019 with the participation of 4394 people aged 50-74. ALT and HDL-C levels were measured using a BT-1500 autoanalyzer. The mean ALT/HDL-C ratio was reported along with 95% confidence intervals (CI). The multiple logistic regression was used to examine the association between this ratio and DM, while controlling for the effects of other independent variables. The mean and standard deviation of the ALT/HDL-C ratio in all participants were 16.62 ± 11.22 (95% CI 16.28-16.96). The prevalence of DM was 34.7% and individuals with DM had a mean ALT/HDL-C ratio that was 1.80 units higher than those without diabetes (P < 0.001). Also, in individuals with DM, the HDL-C was found to be 0.035 (mmol/L) lower (P < 0.001), while ALT was 1.13 (IU/L) higher (P < 0.001) compared to those without diabetes. Additionally, after controlling for confounding factors, the odds of developing DM increased in a non-linear manner with an increase in the ALT/HDL-C ratio. Abdominal obesity, advanced age, female gender, and hypertension were also found to be associated with increased odds of DM. In conclusion, an increase in the ALT/ HDL-C ratiowas associated with higher odds of DM. This ratio can serve as an important predictor for diabetes mellitus.

A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.

BACKGROUND: Common variants of the max-like protein X (MLX)-interacting protein-like (MLXIPL) gene, encoding the transcription factor carbohydrate-responsive element-binding protein, have been shown to be associated with plasma triglyceride levels. However, the role of these variants in steatotic liver disease (SLD) is unclear. METHODS: We used a genome-first approach to analyze a variety of metabolic phenotypes and clinical outcomes associated with a common missense variant in MLXIPL, Gln241His, in 2 large biobanks: the UK Biobank and the Penn Medicine Biobank. RESULTS: Carriers of MLXIPL Gln241His were associated with significantly lower serum levels of triglycerides, apolipoprotein-B, gamma-glutamyl transferase, and alkaline phosphatase. Additionally, MLXIPL Gln241His carriers were associated with significantly higher serum levels of HDL cholesterol and alanine aminotransferase. Carriers homozygous for MLXIPL Gln241His showed a higher risk of SLD in 2 unrelated cohorts. Carriers of MLXIPL Gln241His were especially more likely to be diagnosed with SLD if they were female, obese, and/or also carried the PNPLA3 I148M variant. Furthermore, the heterozygous carriage of MLXIPL Gln241His was associated with significantly higher all-cause, liver-related, and cardiovascular mortality rates. Nuclear magnetic resonance metabolomics data indicated that carriage of MLXIPL Gln241His was significantly associated with lower serum levels of VLDL and increased serum levels of HDL cholesterol. CONCLUSIONS: Analyses of the MLXIPL Gln241His polymorphism showed a significant association with a higher risk of SLD diagnosis and elevated serum alanine aminotransferase as well as significantly lower serum triglycerides and apolipoprotein-B levels. MLXIPL might, therefore, be a potential pharmacological target for the treatment of SLD and hyperlipidemia, notably for patients at risk. More mechanistic studies are needed to better understand the role of MLXIPL Gln241His on lipid metabolism and steatosis development.

Associations between non-insulin-based insulin resistance indices and heart failure prevalence in overweight/obesity adults without diabetes mellitus: evidence from the NHANES 2001-2018.

BACKGROUND: The triglyceride glucose (TyG) index and triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio are recognized as simple non-insulin-based insulin resistance indices. Our study aimed to explore the relationship between these two indicators and heart failure (HF) in overweight or obesity individuals without diabetes. METHODS: This cross-sectional study selected 13,473 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 dataset. Weighted multivariable logistic regression and subgroup analysis were employed to evaluate the relationships between TyG index, TG/HDL-C ratio, and HF prevalence, respectively. Additionally, smooth curve fitting was utilized to analyze the dose-response relationships. RESULTS: A total of 13,473 obesity or overweight people without diabetes were included in this study through screening, among whom 291 (2.16%) had comorbid HF. The results of multivariable logistic regression suggested that the highest TyG index (OR = 2.4, 95% CI = 1.4-4.2, p = 0.002) and the highest TG/HDL-C ratio (OR = 1.2, 95% CI = 1.1-1.3, p < 0.001) both increased the prevalence of HF, especially in the non-Hispanic population. Dose-response relationships suggested nonlinear relationships between these two indicators and HF. CONCLUSION: Our study demonstrated that elevated TyG index and TG/HDL-C ratio were closely associated with the prevalence of HF, and both exhibited nonlinear relationships with HF prevalence in overweight/obesity adults without diabetes. Based on these findings, additional prospective studies are needed for further validation.